Journal of Clinical and Cellular Immunology
Open Access
ISSN: 2155-9899
ISSN: 2155-9899
Sandra Jovic
Posters-Accepted Abstracts: J Clin Cell Immunol
Cystic fibrosis (CF) is characterized by severe and longstanding bacterial infections of the airways. In addition, there is a chronic and dysregulated inflammation characterized by a massive influx of neutrophils to the lungs. Even though the cause of the disease is known (i.e. mutations in the CFTR gene), the mechanisms resulting in the compromised host defense are not fully understood. The glycoprotein osteopontin (OPN) plays a key role in several states of disease associated with inflammation, for example by recruitment of neutrophils but its expression and possible roles in CF have hitherto not been investigated. In this study, upregulation of OPN was detected in bronchial epithelial cells and in sputum of CF patients. In vitro, OPN bound to the ELR-negative antibacterial chemokines MIG/CXCL9, IP-10/CXCL10 and I-TAC/CXCL11 through electrostatic interactions. In contrast, no binding was found to the neutrophil-recruiting ELR-positive chemokines GRO-β/ CXCL2, GCP-2/CXCL6 and IL-8/CXCL8. Functional consequences of the binding were that OPN inhibited the bactericidal activity of MIG/CXCL9, IP-10/CXCL10 and I-TAC/CXCL11 and also reduced their activation of the CXCR3-receptor that is expressed on NK cells and cytotoxic T cells. In contrast, OPN did not reduce the receptor-activating properties of GRO-β/ CXCL2, GCP-2/CXCL6 and IL-8/CXCL8 against neutrophils. Taken together, upregulation of the neutrophil-recruiting glycoprotein OPN in CF may contribute to the dysregulated inflammation seen in CF, resulting in impaired host defense activities of ELR-negative chemokines (that serve as innate antibiotics and recruit NK cells and cytotoxic T cells), instead promoting an excessive influx of neutrophils, contributing to progress of the disease.